Fortunately, the understanding of the neurophysiologic mechanisms by which noxious and non-noxious stimuli are perceived has substantially improved over the last few years and new drugs and techniques have been developed to treat pain. However, the mechanisms of transmission and perception of pain are not entirely understood and patients still have a great deal of pain while in the hospital and many others have debilitating chronic pain over the course of their lives. Pain still is the most common reason why patients seek health care and usually is the consequence of tissue damage that occurs during or after medical illness, surgery, or trauma including chemical and thermal injuries. In order to study the mechanisms of the transmission of noxious stimuli, we have developed a non-injurious neuro-specific nociceptive assay in mice. We use a neuro-stimulator that is used for the diagnosis of pain syndromes and neurologic diseases in humans. This neurostimulator delivers electrical stimuli to the skin at different frequencies and intensities, and produces transient discomfort without producing injury. Unlike currently used pain models that may produce some tissue-injury in order to induce pain, this assay is non-injurious and adds an invaluable tool for the study of the mechanisms of pain. We use a method that does not stimulate the peripheral cutaneous nerve organ used for the transmission of a painful stimulus (nociceptors), does not produce tissue-injury, and yet produces transient discomfort and pain-avoiding behavior by stimulating specific nerve fibers. We completed all pilot studies for the development of a non-injurious neuro-specific nociceptive assay in mice, developed normative values for the response to each frequency, and have fully developed a software application to control the neuro-stimulator, and automate a large portion of the protocol. We are now studying the impact of aging as well as the role of neuronal nitric oxide in the transmission of noxious stimuli in specific nociceptive nerve fibers. Ongoing investigations will serve to further validate the model and demonstrate its value for studies of the mechanisms of pain. Ultimately, the assay could serve as a valuable tool to study the pharmacodynamics of new therapeutic agents to treat pain.